Current research of membrane-associated ring finger –C3HC4-1 (MARCH1) suggests that its role in mammalian immunity is more complex than was previously thought. MARCH1 is an E3 ubiquitin ligase expressed by antigen-presenting cells of the immune system, where it inhibits antigen presentation by downregulation of its substrates, MHC class II and CD86. We have studied how MARCH1 expression is regulated and determined that the protein levels are regulated, in part, through its inherent instability. We have shown that MARCH1 has distinct regions responsible for both its stability and function. The amino terminus contains a region needed for destabilization of the protein, while the amino acid residues 229-257 are missing: it appears to lead to a loss of function. Preliminary studies into dysregulation of antigen processing, inhibited by loss of MARCH1 expression in mice, have shown inclinations toward a metabolically diseased state. Knock-out (KO) MARCH1 mice have increased amounts of visceral adipose tissue relative to wild type. In addition, our preliminary results, examining transcript levels, suggest that a pro-inflammatory environment may result from the loss of MARCH1 in these fat depots, potentially resulting in metabolic disease. Our results indicate that changes in MARCH1 levels lead to a potentially dysregulated inflammatory environment.

Current research of membrane-associated ring finger –C3HC4-1 (MARCH1) suggests that its role in mammalian immunity is more complex than was previously thought. MARCH1 is an E3 ubiquitin ligase expressed by antigen-presenting cells of the immune system, where it inhibits antigen presentation by downregulation of its substrates, MHC class II and CD86. We have studied how MARCH1 expression is regulated and determined that the protein levels are regulated, in part, through its inherent instability. We have shown that MARCH1 has distinct regions responsible for both its stability and function. The amino terminus contains a region needed for destabilization of the protein, while the amino acid residues 229-257 are missing: it appears to lead to a loss of function. Preliminary studies into dysregulation of antigen processing, inhibited by loss of MARCH1 expression in mice, have shown inclinations toward a metabolically diseased state. Knock-out (KO) MARCH1 mice have increased amounts of visceral adipose tissue relative to wild type. In addition, our preliminary results, examining transcript levels, suggest that a pro-inflammatory environment may result from the loss of MARCH1 in these fat depots, potentially resulting in metabolic disease. Our results indicate that changes in MARCH1 levels lead to a potentially dysregulated inflammatory environment.

en_US

dc.type

text

en_US

dc.type

Electronic Thesis

en_US

thesis.degree.name

B.S.

en_US

thesis.degree.level

bachelors

en_US

thesis.degree.discipline

Honors College

en_US

thesis.degree.discipline

Molecular and Cellular Biology

en_US

thesis.degree.grantor

University of Arizona

en_US

dc.contributor.advisor

Lybarger, Lonnie

-

All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.